FR2984743A1 - COSMETIC USE OF STEVIOL, STEVIOL GLYCOSIDE DERIVATIVE, OR ONE OF THEIR ISOMERS FOR STIMULATING, RESTORING OR REGULATING METABOLISM OF SKIN CELLS AND SEMI-MUCOUS MEMBRANES - Google Patents

Abstract

The present invention relates to the cosmetic use of steviol, a glycoside derivative of steviol, or an isomer thereof, for stimulating, restoring or regulating the metabolism of skin cells.

Description

The invention relates to the field of cosmetic active agents, and more particularly to active agents dedicated to acting with regard to aging of the skin. The human skin consists of several compartments, three of which cover the whole body, namely a superficial compartment, the epidermis, the dermis and a deep compartment, the hypodermis. The epidermis is a keratinized stratified squamous epithelium. It consists mainly of keratinocytes, but also other cells, and is based on a basement membrane that separates it from the dermis. The dermis is a connective tissue. Its architecture results from the arrangement and the interactions between the constituents of the extracellular matrix and the fibroblasts which ensure their synthesis and their degradation. It constitutes the main mass of the skin. The dermis is subdivided into two layers, papillary and reticular. The dermis consists of collagen fibers and elastic fibers as well as glycosaminoglycans and proteoglycans. These different structures form a complex network that plays a key role in the biomechanical properties of the skin. Finally, the hypodermis, the deepest and usually the thickest compartment of the skin, is invaginated in the dermis and is attached to the underlying dermis by collagen and elastin fibers. It consists essentially of a type of cells specialized in the accumulation and storage of fat, adipocytes. In the area where the integumentary coating is not keratinized, the epidermis is called mucosa. This epithelium also contains fibroblasts within a dermal matrix. The skin tissue also includes appendages, such as sweat glands, pilosebaceous follicles, hair, hair, and nails. During chronological and / or photoinduced aging, the skin, and more particularly the dermis, undergoes numerous modifications and degradations. In particular, numerous alterations of the skin, resulting from a dysfunction of its homeostasis, and in particular a dysfunction of fibroblast metabolism, occur. At the cellular level, aging results in an alteration of the physiology or metabolism of the main cell types of the dermis, in particular fibroblasts, and the epidermis, such as keratinocytes. At the tissue level, aging is manifested by a disorganization of the architecture of the epidermis, the dermal-epidermal junction of the dermis, as well as blood supply and innervation systems, a slowing down of different metabolisms such as those put into play in the balance of the barrier function. This deregulation of the cell metabolism of the skin cells, and in particular the fibroblasts, can result in an alteration of the microrelief, an appearance of wrinkles and fine lines, an alteration of the mechanical properties of the skin with a decrease in the firmness and the elasticity or an alteration of the radiance of the complexion of the skin and its apparent age. Histologically, a flattening of the dermal-epidermal junction and a decrease in the thickness of the dermis are observed. What is more, the alteration of the mechanical properties of the skin can be accentuated by various secondary factors, such as the consequence of various physiological disorders, such as for example metabolic diseases, hypo or hypersecretion of hormones, vitamin deficiency or disorder of gene expression, environmental aggressions, such as pollution or radiation, extrinsic factors, such as tobacco, inflammation, organizational variations, density of hypodermis, following a modification body mass, pregnancy, a state of obesity, cellulite, drug treatments, with topical corticosteroids for example, or even disorganization of the constituents of the extracellular matrix resulting for example from stretch marks, scars or bedsores . Also, at the menopause, the dermis can be altered by a decrease in its dermal thickness and one can note an accentuation of the fine lines and wrinkles of surface. The skin then has a rough appearance on palpation and reduced flexibility. From the foregoing, it is understood that it is important to have products capable of acting effectively on the cells of young or aged skin in order to limit the deterioration of their functionalities and their aging, and in particular on fibroblasts, to prevent , reduce and / or treat signs of aging of the skin. The object of the present invention is to satisfy these needs. Unexpectedly, the inventors have observed that a steviol, a glycoside derivative of steviol, or one of their isomers, is particularly useful for preventing or treating disorders related to cutaneous aging, whether chronobiological or photobiological. Indeed, as is apparent from the examples below, the inventors have unexpectedly found that a steviol, a glycoside derivative of steviol, or one of their isomers, effectively induces contraction of fibroblasts. It follows from this contraction of fibroblasts densification of the dermis which, for obvious reasons, can prevent and / or treat deep wrinkles and loss of firmness of the skin, to control the homeostasis of the skin and stimulate its regeneration to fight against the appearance of signs of aging of the skin, whether they are chronological and / or photoinduced. Thus, according to a first of its aspects, the subject of the invention is the use, in particular cosmetic use, of steviol, of a glycoside derivative of steviol, or one of their isomers, for stimulating, restoring or regulating the metabolism of the skin and semi-mucous membranes, preferably dermal cells, and more particularly fibroblasts. For the purposes of the present invention, the term "metabolism" is intended to denote all the molecular and energetic transformations that take place in a living cell and contribute to its homeostasis, that is to say to its maintenance of biological activity and physiological balance.

According to another of its aspects, the subject of the invention is the use, in particular cosmetic use, of steviol, of a glycoside derivative of steviol, or one of their isomers, for preventing and / or treating the signs of aging of the skin. and semi-mucous membranes. For the purposes of the present invention, the term mucosa refers in particular to the lips.

By "signs of aging of the skin" is meant, within the meaning of the invention, any changes in the external appearance of the skin due to aging, whether chronobiological and / or photoinduced, such as for example wrinkles and fine lines, wilted skin, soft skin, thinned skin, lack of elasticity and / or tone of the skin, lack of density and / or firmness of the skin, but also any internal changes in the skin which do not automatically result in a modified external appearance, such as all internal skin damage resulting from exposure to ultraviolet radiation. To the inventors' knowledge, the anti-aging activity of steviol, of a glycoside derivative of steviol, or one of their isomers, has, to date, never been described.

Admittedly, these compounds have already been proposed as a sweetener (EP 1 856 967), promoter of the solubilization of compounds not or only slightly soluble in aqueous medium (WO 2009/126950). The scientific literature further suggests that rebaudioside A could be a molecule of interest for regulating glucose or metabolism of pancreatic cells and treating diabetes (Abudula et al., Metabolism, 2004, 53: 1378; WO 02 / 060419), for improving cognitive functions (WO 2009/071277), or for treating cardiovascular diseases (WO 2008/134828).

Similarly, some authors also describe their use in particular for treating oily skin or acne by regulating the metabolism of sebocytes (US 5110801) or even for combating inflammatory phenomena (allergy, dermatitis) (IP-08325156). -AT). Finally, WO 07/094312 proposes the use of steviosides to promote the penetration of vitamin C into cells.

However, until now, no direct effect on dermal cells (fibroblasts) or effect on semi-mucous membranes accessible topically other than the production of sugary sensations has been demonstrated. The subject of the invention is also the use, in particular cosmetic use, of steviol, of a glycoside derivative of steviol, or one of their isomers, for preventing, reducing and / or treating wrinkles, fine lines or an alteration of the microrelief. The subject of the invention is also the use, in particular cosmetic use, of steviol, of a glycoside derivative of steviol, or one of their isomers, for reinforcing the mechanical properties of the skin and semi-mucous membranes, in particular for combating wilted, soft, distended, sagging and / or thinned skin, and / or strengthening and / or restoring the elasticity or firmness of the skin. The subject of the invention is also the use, in particular cosmetic use, of steviol, of a glycoside derivative of steviol, or one of their isomers, for preventing an alteration of, and / or maintaining skin and semi-homeostasis. -muqueuses. The subject of the invention is also the use, in particular cosmetic use, of steviol, of a glycoside derivative of steviol, or one of their isomers, for preventing and / or treating cutaneous lesions related to menopause. For the purposes of the present invention, the term "to prevent" the fact of reducing at least partly the risk of manifestation of a given phenomenon, ie in the present invention the alterations of the metabolism of aged cells of the skin and / or the signs of aging of the skin, and in particular those defined previously. According to another of its aspects, the invention is directed to steviol, a glycoside derivative of steviol, or one of their isomers as an agent, in particular a cosmetic or dermatological agent, for stimulating, restoring or regulating the metabolism of skin cells and semimuqueuses. It also relates to steviol, a glycoside derivative of steviol, or one of their isomers, for preventing and / or treating signs of aging of the skin or semi-mucous membranes. It also relates to steviol, a glycoside derivative of steviol, or one of their isomers as an agent, in particular a cosmetic or dermatological agent, for preventing, reducing and / or treating wrinkles, fine lines or an alteration of the microrelief. It also relates to steviol, a glycoside derivative of steviol, or one of their isomers, as an agent, in particular a cosmetic or dermatological agent, for reinforcing the mechanical properties of the skin and semi-mucous membranes, in particular for fighting the skin. wilted, soft, distended, sagging and / or thinned, and / or strengthening and / or restoring the elasticity or firmness of the skin. It also relates to steviol, a glycoside derivative of steviol, or one of their 15 isomers as an agent, in particular a cosmetic or dermatological agent, for preventing an alteration of and / or maintaining the homeostasis of the skin or of the semi-mucous membranes . It also relates to steviol, a glycoside derivative of steviol, or one of their isomers as an agent, in particular a cosmetic or dermatological agent, for preventing and / or treating cutaneous lesions related to menopause. According to another of its aspects, the present invention relates to a cosmetic or dermatological composition comprising at least an effective amount of steviol, a glycoside derivative of steviol, or one of their isomers, especially as defined below in combination with at least one additional active agent selected from a sweetening agent, an amino acid, a peptide, an extracellular calcium receptor agonist, a calcium channel agonist, an anti-wrinkle active agent, an anti-aging active agent, an agent moisturizer, an antioxidant, a photoprotective agent, and mixtures thereof. According to yet another of its aspects, the present invention is directed to a kit comprising at least one container containing a composition comprising steviol, a steviol glycoside derivative, or one of their isomers, and at least one device arranged to allow the administration of said composition to an individual, and / or to increase the effectiveness of said composition in an individual, and / or to promote topical penetration in an individual of said composition.

As is apparent from what follows, this device can be adjusted to an intracutaneous injection in the image of a syringe, an implant or microneedles. It may also be an ultrasonic device or iontophoresis, or a light or thermal device.

According to yet another of its aspects, the present invention is directed to a method, in particular a cosmetic method, for stimulating, restoring or regulating the metabolism of skin or semi-mucous cells comprising at least one administration step, to an individual in need thereof, at least one effective amount of steviol, a glycoside derivative of steviol, or one of their isomers.

According to yet another of its aspects, the present invention is directed to a method, in particular a cosmetic method for preventing and / or treating signs of aging of the skin or semi-mucous membranes comprising at least one administration step, to an individual in need thereof, at least one effective amount of steviol, a glycoside derivative of steviol, or one of their isomers.

As is apparent from the following, steviol, a glycoside derivative of steviol, or one of their isomers can be administered topically externally, intra- cutaneously, intradermally or subcutaneously, orally and preferably by external topical. The present invention relates to the use of a main active ingredient selected from a steviol, a steviol glycoside derivative, or an isomer thereof. Steviol is represented by formula (I): OH H (I) Steviol is the precursor common to steviol glycosides. By "precursor" is meant, within the meaning of the present invention, any compound participating in a reaction that produces one or more other compounds.

By "steviol glycoside derivative" is meant any compound represented by the formula (II): CH 2 (II) in which R 1 and R 2, respectively located at the level of the C 19 and C 13 carbons of the formula (II) represent, independently of one of the other, the hydrogen atom or a sugar residue, linear or branched, cyclized or not. Preferably, R1 and R2 are different from hydrogen. In particular, R1 and R2, identical or different and preferably different, represents a sugar residue consisting of one or more glucose and / or rhamnose entities.

By way of illustration and not limitation of these sugar residues may be mentioned the groups consisting of - a single entity of sugars, in particular Glu glucose, - a sequence of two sugars in the image of a diholoside such as a sequence of two glucose entities, or - a sequence of three sugar units in the image of a linear or branched and preferably branched triholoside such as, for example, a branched radical formed of three glucose units and a branched radical formed by an entity glucose substituted with a glucose moiety and a rhamnose moiety. According to a particular variant, R 1 represents a glucose entity.

In a more preferred embodiment, R1 represents a glucose unit and R2 a branched triholoside. Table I below shows the detailed structure of certain steviol glycoside derivatives of formula (II) that are suitable for the invention. R1 R2 stevioside Glu Glu-Glu rebaudioside A Glu Glu-Glu Glu rebaudioside C Glu Glu-Rha Thus, a glycoside derivative of steviol according to the invention may be chosen from stevioside, rebaudioside A, rebaudioside C (or dulcoside B), dulcoside A, rebaudioside B, cyclobenzene, and the like. rebaudioside D, rebaudioside E, rebaudioside F, steviolbioside, rubusoside, and mixtures thereof. More preferably, a glycoside derivative of steviol according to the invention is chosen from stevioside, rebaudioside A, rebaudioside C (or dulcoside B), dulcoside A, and mixtures thereof. Even more preferentially, a steviol glycoside derivative according to the invention is rebaudioside A. For the purposes of the present invention, the term "isomer" is intended to denote at least two molecules having the same formula but having semi-developed formulas or different formulas developed. Isomerviol, represented by the following formula (III), may especially be mentioned as the isomer according to the invention: (III) The present invention naturally implements an effective amount of steviol, a steviol glycoside derivative, or isomers of these so as to obtain the desired effect. This effective amount may vary with regard to various parameters such as, in particular, the target indication, the characteristics of the individual treated, the galenic formulation adopted, the nature of the formulation excipients, or the presence of ancillary active ingredients. (s). For the purposes of the present invention, the term "effective amount" means a sufficient and necessary amount of a given active to exert the desired effect, namely in the present invention stimulate, restore or regulate the metabolism of skin cells , especially fibroblasts, or to prevent, reduce and / or treat the signs of aging of the skin. Such an amount can be determined by any method known to those skilled in the art, for example by means of in vitro, ex vivo or in vivo tests, such as clinical trials. To give an order of magnitude, it is possible to use steviol, a glycoside derivative of steviol, or an isomer thereof in a composition in a proportion of 0.01 to 50% by weight, preferably from 0.05 to 30% by weight. by weight, in particular from 0.1 to 10% by weight and more preferably from 0.5 to 5% by weight, relative to the total weight of the composition. According to a preferred embodiment, a main active agent according to the invention, that is to say steviol, a glycoside derivative of steviol, or one of their isomers, is used in the form of an extract of less a plant of the genus Stevia.

The use of the main active agent according to the invention in the form of an extract of at least one plant of the genus Stevia is particularly advantageous in that it makes it possible to propose a novel cosmetic active ingredient of natural origin and thus, to meet a growing consumer demand in this direction. The genus Stevia belongs to the family Asteraceae, which includes 150 to 200 species of aromatic herbs or shrubs, some of which contain natural sweeteners. Stevia are native to tropical regions of Latin America. According to the invention, the extract of a plant of the genus Stevia can be chemically modified (it is then semisynthetic), but it is preferably natural.

An extract of a plant of the genus Stevia, within the meaning of the present invention, may be prepared from any plant material derived from said plant or its cells grown according to traditional methods or by in vivo biotechnology or from in vitro culture.

In vivo culture is understood to mean any culture of conventional type, ie in soil in the open air or in the greenhouse or above ground. By in vitro culture is meant all the techniques known to those skilled in the art which artificially allows the production of a plant or part of a plant. The selection pressure imposed by the physicochemical conditions during the growth of the plant cells in vitro makes it possible to obtain standardized plant material that is available throughout the year, unlike plants grown in vivo. An extract of a plant of the genus Stevia used in the present invention can be obtained from any plant material derived from this whole plant or from any part of this plant, such as for example leaves, stems, flowers and plants. flowering tops, seeds, buds and roots, undifferentiated cells or plant stem cells. Preferably, an extract of a plant of the genus Stevia according to the invention is obtained from the leaves.

Even more preferably, an extract of a plant of the genus Stevia according to the invention comes from a plant of the species Stevia rebaudiana (Bertoni), also called Eupatorium rebaudianum or "hemp water". Such a species is now cultivated in many countries and on continents other than Latin America, notably in Singapore, Taiwan, Malaysia, South Korea, China, Israel, or Australia. Preferably, an extract of a plant of the genus Stevia according to the present invention is used in a composition in a proportion of 0.00001% to 50% by weight, preferably from 0.0001% to 10% by weight, and preferably from 0.01% to 4% by weight, relative to the total weight of said composition.

Steviols are already commercially available. As rebaudioside A that may be used in the present invention, mention may especially be made of Stevia extract containing 99% of rebaudioside A marketed by Blue California under the name Good'n sweetTM as well as Stevia extract containing 97% A rebaudioside A sold by the company CHENGDU WAGOTT PHARMACEUTICAL under the name ViaSweetTM It may also be the yeast fermented Stevia extract described in WO2003 / 035090.

The properties inherent to a main active agent according to the invention, that is to say a steviol, a glycoside derivative of steviol, or one of their isomers, are such as to allow the use, within a composition according to the invention, compounds or assets usually unusable because difficult to formulate, solubilize, deliver in a controlled manner, or to vectorize. Thus, as indicated above, an extract according to the invention may advantageously be associated with at least one additional active agent chosen from a sweetening agent, an amino acid such as, for example, glycine, a peptide, inosine or a derivative thereof, guanosine or a derivative thereof, an extracellular calcium receptor agonist, a calcium channel agonist, an anti-wrinkle active agent, an anti-aging active agent, a moisturizing agent, an antioxidant, a photoprotective agent and their mixtures. Preferably, an additional active agent may be chosen from a sweetener, an amino acid, a peptide, inosine or a derivative thereof, guanosine or a derivative thereof, an extracellular calcium receptor agonist, a calcium channel agonist, and mixtures thereof. Preferably, an additional active agent may be chosen from an anti-wrinkle active agent, an anti-aging active agent, a moisturizing agent, an antioxidant, a photoprotective agent, a sunscreen, in particular a UV filter, and mixtures thereof. Sweeteners considered as an additional asset may be qualified as a secondary sweetener in that they are necessarily distinct from the main active ingredient according to the present invention. As a secondary sweetener, mention may be made of those of natural or biotechnological origin, such as saccharide or polysaccharide polyols or amino molecules, in particular thaumatin or extract from the arils of Thaumatococcus daniellii or katemfe, or their analogs, precursors, or synthetic or semisynthetic derivatives. It can also be mentioned "high intensity sweeteners", such as xylitol (in C5), erythritol (in C4), sucralose, neohesperidin dihydrochalcone or NHDC (E959) and "bulk sweeteners", such as sorbitol, maltitol, isomalt, mannitol, lactitol, glycerol and its derivatives, fructose and its derivatives, maltose and its derivatives, sucrose and its derivatives, glucose and its derivatives, mannose and derivatives , as well as simple dares especially those of natural or biotechnological origin. Mention may also be made of saccharin, acesulfame potassium (or acesulfame K), and cyclamate (or sodium cyclamate).

For the purposes of the present invention, the term "amino acids" is understood to mean, in particular, glutamate or N-Me-D-aspartate, in particular as described in WO 2009/071277, as well as the calcium channel activators described in WO 2008/139946. It may also be taurine, glutamine, arginine, citrulline, glycine, serine, and N-acetyl-cysteine. The choice and the content of these additional assets depend in particular on the route of administration considered which fall within the competence of those skilled in the art. These additional active agents may be present in a composition according to the invention in a content ranging from 0.001 to 50% by weight, preferably from 0.01 to 10% by weight, and more preferably from 0.01 to 5% by weight. relative to the total weight of the composition comprising them. Advantageously, the active ingredient according to the invention, namely steviol, the glycoside derivative of steviol, or one of their isomers, mixed with or not with other additional active (s) may be formulated in a cosmetic or dermatological composition. Preferably, a composition of the invention is a cosmetic composition.

According to a first variant embodiment, the main active agent according to the invention is intended for topical administration. Thus, the compositions containing the main active agent according to the invention may be in the form of skincare or semi-mucous products such as a protection, treatment or care composition for the face, for the lips , for the hands, for the feet, for the anatomical folds or for the body (for example day creams, night cream, makeup remover, make-up base, sunscreen composition, body protection or care milk, milk after -solar, lotion, gel or mousse for the care of the skin or scalp, serum, powder, mask, artificial tanning composition, aftershave composition, hair composition, product for the armpit area, product for hygiene and According to a second variant embodiment, the main active agent according to the invention is intended for oral administration.

Thus, the composition of the invention may be in any suitable form, particularly in the form of an oral solution, a beverage, a tablet, a capsule, a capsule or a nutritional food or nutritional supplement.

According to a third variant embodiment, the main active agent according to the invention is intended for administration by the intracutaneous route such as the intradermal or subcutaneous route. This administration may for example be carried out by means of a device for intra-cutaneous injection (syringe, implant or reservoir and micro-needles) or an ultrasonic device or iontophoresis, see a light or thermal device. Such administration may also be effected by mesotherapy. The intracutaneous use of a composition of the invention is to be distinguished from a surgical procedure and is intended only to provide a surface treatment of the skin for aesthetic, protective, restorative or comfort purposes. In other words, the intra-cutaneous route of administration, in the present invention, only results in a superficial break-up of the skin and therefore goes out of any medical, surgical, or therapeutic setting. For the intracutaneous route, alternatively, topical patch administration may be preferred. Preferably, a main active agent according to the invention is intended for topical administration, that is to say by surface application of the keratin material in question. Preferably, a main active ingredient according to the invention, when present in a composition, can be formulated in a physiologically acceptable medium. Within the meaning of the present invention, the term "physiologically acceptable medium" means a medium that is suitable for the administration of a composition topically, orally, or intradermally, such as the intraepidermal, intradermal or subcutaneous. A physiologically acceptable medium is preferably a cosmetically or dermatologically acceptable medium, that is to say without odor, or unpleasant appearance, and which is perfectly compatible with the route of administration considered.

When the composition is intended to be administered topically, that is to say by surface application of the keratin material in question, such a medium is considered physiologically acceptable when it does not generate tingling, tightness or redness that is unacceptable for the user.

When the composition is intended to be administered orally, such a medium is considered physiologically acceptable when it does not generate digestive intolerance. Moreover, when the composition is intended to be administered intradermally, such a medium is considered physiologically acceptable when it does not generate a reaction felt as unpleasant by the user, for example tingling, tugging or redness, even does not generate reactions of inflammation, allergy, edema or pruritus. The composition according to the invention may be in any galenical form normally used in the cosmetic and dermatological fields.

It may especially be in the form of an aqueous, aqueous-alcoholic, oily or optionally gelled solution, a dispersion of the lotion type optionally two or three-phase, an oil-in-water or water-in-oil or multiple emulsion, an aqueous gel, an oil dispersion in an aqueous phase, in particular with the aid of spherules, these spherules possibly being polymeric particles or, better still, lipid vesicles of ionic and / or nonionic type, or still in the form of a powder, a serum, a paste, a solid cake delitable by friction of an applicator or a stick or stick flexible or rigid and fuse on the skin or semi- mucous membranes. It can be of solid consistency, pasty, or liquid more or less fluid. With regard to the pharmaceutical formulation considered, the active agent according to the invention can be formulated with the constituents of use. By way of non-limiting illustration of these usual components, mention may be made especially of water, solvents, volatile or non-volatile oils, in particular as detailed below, waxes, in particular as described below, pigments, fillers, surfactants, gelling agents, preservatives, dyestuffs, antioxidants, UV filters and mixtures thereof. Of course, those skilled in the art will take care to choose the optional additional compound (s), and / or their quantity, in such a way that the advantageous properties of the main active agent according to the invention are not, or not substantially, impaired by the addition envisaged and that the properties of the resulting compositions are compatible with the preferred route of administration. A composition according to the invention may advantageously be in the form of an emulsion, in particular obtained by dispersing an aqueous phase in a fatty phase (W / O) or a fatty phase in an aqueous phase (O / W). , of liquid or semi-liquid consistency of the milk type, or of soft, semi-solid or solid consistency of the cream or gel type, or of multiple emulsion (W / O / W or W / E / H). These compositions are prepared according to the usual methods.

Thus, a composition according to the invention may advantageously comprise from 0.1 to 99.9% by weight, and preferably from 30 to 95% by weight of water, relative to the total weight of said composition. A composition according to the invention may also advantageously comprise at least one liquid fatty phase at room temperature and atmospheric pressure. The amount of oily phase present in the compositions according to the invention may range, for example, from 0.01 to 50% by weight and preferably from 0.1 to 30% by weight relative to the total weight of the composition. As examples of oils that can be used in the composition according to the invention, mention may be made of hydrocarbon-based oils of animal origin, hydrocarbon-based oils of vegetable origin, esters and synthetic ethers, in particular of fatty acids, hydrocarbons. linear or branched, of mineral or synthetic origin, fatty alcohols and silicone oils and mixtures thereof. Other fatty substances which may be present in the oily phase are, for example, waxes and fatty acids containing from 8 to 30 carbon atoms, such as stearic acid, lauric acid, palmitic acid and acid. oleic. These fatty substances may be chosen in a varied manner by those skilled in the art in order to prepare a composition having the properties, for example of desired consistency or texture. Similarly, a composition according to the invention may further comprise at least one dyestuff chosen for example from pigments, nacres, dyes, effect materials and mixtures thereof.

These dyestuffs may be present in a content ranging from 0.01% to 50% by weight, preferably from 0.01% to 30% relative to the total weight of the composition. A composition according to the invention may further comprise at least one filler, in particular in a content ranging from 0.01% to 50% by weight, relative to the total weight of the composition, preferably ranging from 0.01% to 30% by weight. % in weight. These fillers may be mineral or organic and their choice is within the skill of those skilled in the art. As indicated above, the administration of the active agent according to the invention may be carried out via the implementation of a device adjusted to the mode of administration considered, that is to say, topical, oral or intracutaneous. The choice of such devices, made in particular with regard to the type of preferred route of administration falls within the general knowledge of the skilled person. In addition to the devices already described above with regard more particularly to an intracutaneous administration may also be considered: - direct topical delivery devices or by means of a particular applicator such as for example micro-intracutaneous injections, or patches simple or iontophoretic; - Electrical, electromagnetic or magnetic devices for simultaneous physical stimulation to the application of said composition at the application site; devices designed to provide heat and / or cold, thus modifying the electrical signals at certain receivers, for example in the image of the Derm-Ice device; and devices dedicated to providing light, activating or inhibiting certain enzymatic systems. In these last two alternatives, the device contributes to boosting the effectiveness of the asset according to the invention at the site of administration considered. Thus, the present invention also provides a kit comprising at least one container containing a composition comprising steviol, a steviol glycoside derivative, or one of their isomers, and at least one device suitable for administering said composition to an individual and especially as described above.

The present invention further relates to a cosmetic method for stimulating, restoring or regulating the metabolism of skin cells, in particular fibroblasts, comprising at least one step of administering, to an individual in need, at least one effective amount steviol, steviol glycoside derivative, or one of their isomers. The present invention also relates to a cosmetic process for preventing and / or treating signs of aging of the skin comprising at least one step of administering, to an individual in need thereof, at least one effective amount of steviol, glycoside derivative steviol, or one of their isomers. A cosmetic process according to the invention may be carried out on a daily basis, for example on the basis of a single administration per day, or of a divided administration in two or three times a day, for example once in the morning and once in the morning. times in the evening.

Throughout the description, including the claims, the phrase "having one" should be understood as being synonymous with "having at least one", unless the opposite is specified. Expressions "between ... and ..." and "ranging from ..." must be understood as inclusive terms, unless otherwise specified.

The following examples and figures are presented for illustrative and non-limiting purposes of the invention. The percentages are expressed by weight of raw materials. The compounds are, as the case may be, listed in chemical names or CTFA names (International Cosmetic Ingredient Dictionary and Handbook).

Example 1 Influence of Rebaudioside A on the Contraction of Fibroblasts a) Principle of the Test The principle of this test consists of studying the effect of the test product, namely rebaudioside A, on an equivalent dermis model consisting of a collagen matrix. colonized by normal human fibroblasts.

These conditions are intended to mimic in vitro contractile dermal phenomena. Any contraction is represented by a retraction of the collagen gel, thus resulting in a decrease in the total area of the equivalent dermis. The measurement of this surface makes it possible to evaluate the contraction effects of substances previously brought into contact with the equivalent dermis. b) Products used in the test The tested active ingredient is a Stevia extract containing 99% of rebaudioside A marketed by Blue California under the name Good'n sweetTM. The collagen used is collagen type I (commercial solution). It is extracted from skins of young cattle and kept in an acid environment at + 4 ° C; it polymerizes naturally by warming to 37 ° C and decreasing the acidity level. Collagen is previously dialyzed against successive baths of water + acetic acid. The dermal fibroblasts were isolated from human skin explants and cultured in DMEM supplemented with: 10% FCS, 2 mM L-Glutamine, 50 U / ml penicillin, 50 μg / ml streptomycin. They were used in the 5th passage. c) Protocol Several sets of attached equivalent dermas containing normal human fibroblasts are prepared: a control series without any treatment, and series treated with the test compound for each of the following concentrations: 0.001 and 0.01 mg / ml. The dermis equivalents are prepared as described in Asselineau et al., Exp. Cell. Res., 1985, 159, 536-539; Models in Dermatology, 1987, vol 3 pp 1-7, in the following proportions: MEM medium (2X) with or without guanosine: 45% Fetal calf serum: 10% NaOH (0.1N): 5% MEM medium ( 1X): 4% Collagen: 26% Fibroblasts: 10% For each equivalent dermis, the protocol is as follows: in a 50 ml centrifuge tube kept in crushed ice, MEM media are introduced successively in the presence of additives ( Glutamine 1%, Non-essential amino acids 1%, Sodium pyruvate 1%, Fungizone 1% and Penicillin / Streptomycin 1%), fetal calf serum, sodium hydroxide NaOH. Fibroblasts isolated from human skin explants are then added at a concentration of 1.5 × 10 5 cells per 1 ml of culture medium. A volume / volume mixture of collagen in 1/1000 acetic acid is then added slowly against the wall of the tube so as to observe the appearance of a whitish cloud.

The whole is then carefully mixed and distributed in the wells of a 12-well culture plate (Costar type reference 3512) at the rate of 2 ml of mixture per well. The final cell concentration is 3.104 cells / dermis equivalent, with a final collagen concentration of 1 mg / ml.

The culture plate is then placed in an incubator at 37 ° C with 5% CO2. Once formed after polymerization of the collagen equivalent dermes are left adherent to the culture medium for 3 days and then detached from the support so that the contraction can start. These attached equivalent dermes were taken out of the incubator to take the images for the measurement of their surface and for each point of the kinetics of contraction (0, 7, 24 and 48 hours after their detachment). They are immediately returned to the incubator between each measurement point. Dermal Equivalents treated (excluding untreated control) with rebaudioside A, are released from OJ, the day of manufacture, by introducing rebaudioside A at the concentration chosen. Each experimental condition controls, and tests with Rebaudioside A were performed in n = 3. The lattices are then incubated for 7 days with change of the culture medium and photograph plates at 1 '(J1), 3 "ne (J3), 4th (J4) and 7th (J7) day.

The evaluation of the spontaneous contraction of the treated (with the test compound) and the control (without test compound) dermal dermes is carried out by measuring their surface, at different times after the beginning of the spontaneous contraction. This method was simultaneously validated with a positive control. The surface area of the lattices is measured using the software NIS-Elements basic version 3.10. To this surface measurement corresponds a contraction percentage equal to the ratio of the surfaces according to the formula:% contraction = (Sp-Si) / Sp × 100 where: Sp 'represents the surface of a well of the culture plate; it corresponds to the total surface of the equivalent dermis before contraction `Si 'represents the dermal surface equivalent at time i of the kinetics of contraction. d) Results Table I below describes the results obtained in terms of the percentage of contraction of the Dermes Equivalents treated and untreated, at the different times tested. The results are expressed in% relative to the control. Table 1 Treatment (in days) 1 3 4 7 Control 100 100 100 100 (without rebaudioside) Stevia extract with 99% rebaudioside A (marketed by the company Blue California under the name Good'n sweetTM) 0.001 mg / ml 66 88 86 80 0.01mg / m1 67 86 89 8420 e) Conclusion The above results attest to the effectiveness of the extract of Stevia comprising 99% rebaudioside A (and thus rebaudioside A) on the contraction of the equivalent dermes by report to untreated witnesses. This effect extends to at least 7 days of culture, demonstrating the effectiveness of rebaudioside to stimulate, restore or regulate the metabolism of older skin cells and prevent and / or treat the cutaneous signs of aging.

EXAMPLE 2 Anti-Aging Night Rich Emulsion Raw Material (INCI Name)% by Weight Disodium EDTA 0.05 Dimethicone / Vinyl Dimethicone Crosslinked Polymer 1.2 Nylon-12 5 Sodium Styrene Copolymer 0.8 Stevia Extract 99% Rebaudioside A 2.0 (marketed by Blue California Company Good'n SweetTM name) Octanoyl salicylic acid 0.5 Octyl dodecanol 2.00 Cyclopentasiloxane 17.3 Glycerin 23 Propylene glycol 6 Dimethicone 3.8 PEG / PPG-18/18 dimethicone 2, 4 Vegetable oil 3 Phenyl trimethicone 4 Silica 3 Raw material (INCI name)% by weight Preservatives 0.9 Water Qsp 100 Example 3: Global anti-aging perfuming gel Raw material (INCI name)% by weight Potassium hydroxide 1.00 Disodium EDTA 0, Sodium citrate 0.70 Phenoxyethanol 0.4 Caprylic capric triglyceride 2.00 Xanthan gum 0.2 Carbomer 0.3 Polyacrylamide (and) C13-14 isoparaffin (and) laureth-7 2.00 Dimethicone 1.00 Glycerin 5 , 00 Stearic acid 1,00 Glyceryl stearate ( and) PEG-100 stearate 1.00 Stevia extract at 99% rebaudioside A (marketed by Blue California under the name Good'n sweetTM) 0.5 Adenosine 1.00 Salicylic acid 0.20 Water QSP 100 10 Example 4: Day care emulsion Raw material (INCI name)% by weight Xanthan gum 0.4 Potassium hydroxide 0.3 Dimethicone PEG phosphate 2 Stevia extract with 99% rebaudioside A (marketed by Blue California under the name Good'n sweetTM) 0.5 Dicaprylyl carbonate 2.00 Cyclohexasiloxane 10 Salicylic acid 0.5 Ethyl alcohol 15 Water QSP 100 Carbomer 0.4 Polymer acrylate / C10-30 alkyl acrylate 0.25 crosslink Example 5: Intracutaneous formulation: A solution containing 0.005% by weight of a Stevia extract containing 99% rebaudioside A (sold by the company Blue California under the name Good'n sweetTM) in physiological saline is prepared and the whole packaged in sterile bottles. This solution is proposed for injection into the epidermis alone or in admixture with vitamin and trace element preparations. Example 6: Anti-Aging Treatment Powder Raw material (INCI name)% by weight MICA (and) TITANIUM DIOXIDE sold by Merck under the name Timiron® Super Red 117187 0.6 VINYL DIMETHICONE / METHICONE SILSESQUIOXANE CROSSPOLYMER marketed by Shin Etsu under the name KSP100 8 TOCOPHEROL 0.2 Stevia extract containing 99% rebaudioside marketed by Blue California under the name Good'n SweetTM 4 BARIUM SULFATE (and) LAUROYL LYSINE marketed by the company Daito Kasei Kogyo Co., Ltd. under the name LLD-5 BaSO4 (PL) 3 HDI / TRIMETHYLOL HEXYLLACTONE CROSSPOLYMER marketed by the company Toshiki pigment under the name Plastic Powder D400 ACRYLATES COPOLYMER marketed by Akzo Nobel under the name Expancel® Microspheres 551 DE 4 0 D42 0.5 DYE 0.1 ISOCETYL STEARATE 1.5 MICA 8 DIMETHICONE / VINYL DIMETHICONE CROSSPOLYMER marketed by the company Dow Corning under the name DOW CORNING® 9506 POWDER 10 ALUMINUM STARCH OCTENYLSUCCINATE (and) ACRYLATES COPOLYMER (and) MAGNESIUM CARBONATE marketed by the company Akzo Nobel under the name NATRASORB® HFB 15 TALC QSP 100 10 Example 7: Drink to promote protection against skin aging Raw material Quantity Grape juice 5m1 Watermelon juice 2.5m1 Tomato concentrate titrated at 10% by weight lycopene 80mg Taurine 150mg Stevia extract with 99% rebaudioside A (sold by the company Blue California under the name Good'n sweetTM) 250mg Arginine 150mg Vitamin C 150mg Zinc 5mg Vitamin B6 2mg Water QSP 50ml Viamine B12 2mg 10 15 20 25 30

Claims (24)

REVENDICATIONS1. Cosmetic use of steviol, a glycoside derivative of steviol, or one of their isomers, for stimulating, restoring or regulating the metabolism of skin cells and semi-mucous membranes. 2. Cosmetic use of steviol, a glycoside derivative of steviol, or one of their isomers, for preventing and / or treating signs of aging of the skin or semi-mucous membranes. 3. Use according to claim 1 or 2, for preventing, reducing and / or treating wrinkles, fine lines or an alteration of the microrelief 4. Use according to any one of the preceding claims, for reinforcing the mechanical properties of the skin and semi-mucous membranes, in particular for combating wilted, soft, distended, sagging and / or thinned skin, and / or strengthening and or restore the elasticity or firmness of the skin. 5. Use according to any one of the preceding claims, wherein the steviol, the glycoside derivative of steviol, or one of their isomers, is used in a composition in a proportion of 0.01 to 50% by weight, preferably from 0.05 to 30% by weight, in particular from 0.1 to 10% by weight and more preferably from 0.5 to 5% by weight, relative to the total weight of the composition. 6. Use according to any one of the preceding claims, wherein the steviol glycoside derivative is represented by the formula (II): wherein R1 and R2 are independently of one another , the hydrogen atom or a sugar residue, linear or branched, cyclized or not. 30 7. Use according to the preceding claim, wherein R1 and R2, identical or different and preferably different, represents a sucrose residuecomprenant one or more glucose and / or rhamnose entities. Use according to claim 6 or 7, wherein R1 represents a glucose unit and R2 a branched triholoside. 9. Use according to any one of the preceding claims, wherein the glycoside derivative of steviol ischosen among stevioside, rebaudioside A, rebaudioside C, dulcoside A, rebaudioside B, rebaudioside D, rebaudioside E, rebaudioside F, steviolbioside, rubusoside, and mixtures thereof, preferably among stevioside, rebaudioside A, rebaudioside C, dulcoside A, and mixtures thereof, and better is rebaudioside A. 10. Use according to any one of the preceding claims, wherein steviol, the glycoside derivative of steviol, or one of their isomers, is implemented in the form of an extract of at least one plant of the genus Stevia. 11. Use according to the preceding claim, wherein the extract is obtained from the leaves of at least one plant of the genus Stevia, and in particular of the species Stevia rebaudiana. Use according to claim 10 or 11, wherein the extract is used in a composition in an amount of from 0.00001% to 50% by weight, preferably from 0.0001% to 10% by weight, and better from 0.01% to 4% by weight, based on the total weight of said composition Use according to any one of the preceding claims, wherein steviol, the glycoside derivative of steviol, or an isomer thereof, is administered externally, intracutaneously, intradermally or subcutaneously, orally and preferably by external topical route. 14. Steviol, a glycoside derivative of steviol, or an isomer thereof as an agent, in particular a cosmetic or dermatological agent, for stimulating, restoring or regulating the metabolism of skin and semi-mucous cells. 15. Steviol, a glycoside derivative of steviol, or one of their isomers, for preventing and / or treating the signs of aging of the skin or semi-mucous membranes. 16. Steviol, a glycoside derivative of steviol, or an isomer thereof as an agent, in particular a cosmetic or dermatological agent, for preventing, reducing and / or treating wrinkles, fine lines or an alteration of the microrelief. 17. Steviol, a glycoside derivative of steviol, or one of their isomers as an agent, in particular a cosmetic or dermatological agent, for reinforcing the mechanical properties of the skin and semi-mucous membranes, in particular for combating wilted, soft skin, collapsed and / or thinned, and / or strengthen and / or restore the elasticity or firmness of the skin. 18. Steviol, a glycoside derivative of steviol, or one of its isomers as an agent, in particular a cosmetic or dermatological agent, for preventing an alteration of and / or maintaining homeostasis of the skin or semi-mucous membranes. 19. Steviol, a glycoside derivative of steviol, or an isomer thereof as an agent, in particular a cosmetic or dermatological agent, for preventing and / or treating cutaneous lesions related to menopause. 10 20. Cosmetic or dermatological composition comprising at least an effective amount of steviol, a glycoside derivative of steviol, or one of their isomers, in combination with at least one additional active agent chosen from a sweetener, an amino acid, a peptide , an extracellular calcium receptor agonist, a calcium channel agonist, an anti-wrinkle active agent, an anti-aging active agent, a moisturizing agent, an antioxidant, a photoprotective agent, and mixtures thereof. 21. Composition according to the preceding claim, wherein the steviol, the glycoside derivative of steviol, or one of their isomers, is as defined in any one of claims 6 to 11. 22. Kit comprising at least one container containing a composition comprising steviol, a steviol glycoside derivative, or one of their isomers, and at least one device arranged to allow the administration of said composition to an individual, and / or to increase the effectiveness of said composition in an individual, and / or promoting the topical penetration in an individual of said composition. 23. A cosmetic process for stimulating, restoring or regulating the metabolism of skin or semi-mucous cells comprising at least one step of administering, to an individual in need, at least one effective amount of steviol, glycoside derivative of steviol, or one of their isomers. 24. A cosmetic process for preventing and / or treating signs of aging of the skin or semi-mucous membranes comprising at least one step of administering, to an individual in need thereof, at least one effective amount of steviol, glycoside derivative of steviol, or one of their isomers.